2.2 Sedatives, hypnotics, anxiolytics Flashcards
Sedatives fn
decrease activity,
moderate excitement and
calm the recipient
Hypnotics fn
produce drowsiness and facilitate the onset and maintenance of a state of sleep that resembles natural sleep and from which the recipient can be aroused easily
anxiety is cahracterized by
heightened arousal (i.e. physical symptoms such as tachycardia)
accompanied by apprehension, fear, and obsession
anxiety disorders include
phobia/panic disorder,
generalized anxiety disorder,
obsessive compulsive disorder,
post traumatic stress disorder
older anxiolytics and hypnotics like barbiturates fn
depress the CNS in a dose dependent manner, progressively producing sedation, unconsciousness, surgical anesthesia, coma, fatal respiratory cardiac depression
a normal sleep consists of
alternating NREM and REM sleep
NREMstages
4
Sleep cycle
90 min – 4NREM,1REM
– repeats several times during the night
NREM stage 0
awake –from lying down to falling asleep.
Constitutes 1-2% of sleep time
NREM stage 1
dozing–the first stage of NREM seep is drifting off,
it lasts 10 minutes and takes up about 2-5% of normal night sleep
NREM stage 2
the sleeper can be wakened easily,
stage 2 sleep occupies approximately 50% of sleep time
NREM stage 3
much more difficult to awaken,
larger slower delta brain waves are generated
NREM stage 4
during this stage of sleep the body gets its most rest,
very difficult to be awakeng and
sometimes sleep walking (somnabulism) occurs
slow wave sleep (SWS)
stages 3 and 4
during stages 2, 3, and 4
heart rate, BP, and respiration are steady and
muscles are relaxed
REM sleep
brain is extremely active,
brain waves are small and fast with bursts of activity,
REM sleep is characterized by “rapid eye movemt”, and is
the phase when dreams occur most often and intensely
(but dreams can occur at other stages too)
% of sleep in stage 1
5%
% of sleep in stage 2
40-50% — longest
% of sleep in stage 3
12%
% of sleep in stage 4
12%
% of sleep in REM
25%
A hypnotic, at a lower dose
becomes a sedative
classification of these drugs
benzodiazepines,
barbiturates,
benzo receptor agonists,
5HT1A receptor agonist
benzodizepines structure
benzene ring, diazepine ring
benzo TI
high
benzo and anesthsia
cannot induce a state of surgical anesthesia
benzo dependance liablity
low
benzo antidote
flumazenil
benzo and induction
does not induce P450
benzos act by
interacting with the inhibitory GABA a receptors,
has Cl channles,
bind at a distinct site on the receptor
gaba binding to gabaA rec
opening of chlride channel,
leading to hyperpolarization,
increasing the firing threshold, and
decrease generation of action potential
gaba and benzos
binding of gaba is enhanced by benzos resulting in a greater entry of chlroide ion due to
greater freq of opening of the channels, reducing neural excitablity
benzo action
does not directly activate GABA-a rec but REQUIRES GABA to express their effects
GABA facilitatory
Benzodiazepines
benzo and Cl channels
inc frequency of opening of Cl channels
BZD receptors
bzd binds to alpha and gamma subunits in gaba receptor
but NOT with beta subunit
Benzo receptor tyeps
BZ1 BZ2
BZ1
associated with alpha1 subunit.
Mediates sedation (higher dose),
anterograde amnesia,
anticonvulsant action.
Tolerance.
BZ2
associated with alpha2 subunit.
Mediates antianxiety action, (low doses),
muscle relaxation.
No tolerance.
long acting benzo (1-3d)
flur azepam,
di azepam,
chlordi azepoxide,
chlor azepate
intermediate acting benzo (20-20h)
alpr azolam,
lor azepam,
tem azepam
short acting benzo (3-8hrs)
Tri azolam,
Mid azolam,
Ox azepam
Actions of benzos
selective depressant actions,
NOT general depressants like barbiturates
Benzo on CNS
reduction of anxiety (anxiolytic) and aggression at low dose,
sedation and induction of sleep (sedative and hypnotic),
reduction of muslce tone and co-ordination (muslce relaxant),
anti-convulsant effect,
anterograde amnesia (an impairment of memory and recall of envents occuring after the dose is taken)
reduction of anxiety and aggression by benzo
at low doses, benzos are anxiolytics,
reduce anxiety by selectivley inhibiting neuronal circuits in the limbic system of the brain
(BZ2 rec mediate antianxiety and impairment of cognitive functions)
at the the benzo receptor
flumazenil (antagonist) and
zolpidem (sedatives)
can bind
Alprazolam also has
antidepressant actions
Triazolam is reported to produce
agression
tolerance depvelps to
sedative hypnotic property, and
anticonvulsant property,
NOT to anxiolytic property
benzo and sedation and induction of sleep
benzo decreases time taken to get to sleep
(dec sleep latency and hasten onset of sleep),
increase duration of stage 2 NREM,
dec duration of REM sleep,
red intermittent awakening and increase total sleep time,
most subjects wake up with a feeling of refresing sleep,
sedative action is mediated through BZ1R
benzo receptor for sedation
BZ1R
benso receptor for anxiolytic
BZ2R
benzo as a muscle relaxant
BZDs relax the spasticity of skeletal muscle,
probably by increasing presynaptic inhibition in the spinal cord.
At high dose, BZDs depress neuromuscular transmission,
BZDs muscle relaxant effect is independent of sedative action
benzo muscle relaxants
clon azepam,
flunitr azepam,
di azepam
Anticonvulsant effects of benzos
ihibit the development and spread of epileptic seizures in the CNS,
can exert anticonvulsant effects without marked CNS depression, so that mentation and physiologic activity are unaffected,
tolerance develops to anticonvulsant action
anticonvulsant benzos
clon azepam,
di azepam,
nitr azepam, and
flur azepam
respiratory effects of benzos
respiratory suppression occurs at high dose,
however no effect on normal subjects at hypnotic dose
caution of benzos
COPD and asthmatic patients are more prone to respiratory depression,
also caution should be used in pts with cardiac complications
overdose of benzos can cause
death due to depression of medullary respiration center
CVS and Benzo
hypnotic dose in normal subjects will have no CVS effect,
pre-anesthetic dose reduces BP and HR,
Toxic dose leads to circulatory collapse due to depression in myocardial contractility (neg inotropic effect) and vascular tone
GIT and Benzo
decrease nocturnal gastric secretion
Structure of BZDs
lipophilic
bzd and pregancy
benzos cross placental barrier - FLOPPY BABY SYNDROME,
and secreted in the milk
most enzymes are metabolized by
hepatic cyp450 enzyme system to active compunds
– some undergo enterohepatic circulation
bzds that do not have active metabolites and involve only conjugation, preferred in elderly
lor azepam,
ox azepam,
tem azepam
dealkylation and hydroxylation of bzds give rise to
many metabolites, some of which may be active, so biological effects may be much longer than plasma half-life
adverse effects of benzos
relatively safer drug,
monitor incoordination, impairment of mental and motor fn (driving machinery should be avoided), confusion, anterograde amnesia;
increased reaction time,
cognitive performance appears to be affected less than motor performance
contraindication of benzos
pregnancy,
substance abuse,
sleep apnea
chronic use of benzos leadst to
tolerance and
dependance
